Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages

There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other th an their antibacterial properties. In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measuremen t with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determi ned by Northern blotting. Incubation of PAMs with lipopolysaccharide from Escherichia coli and recomb inant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubati on of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cef aclor, These macrolides likewise inhibited the induction of type II NOS mRN A, whereas no inhibitory effects were observed,vith amoxycillin or cefaclor . These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airwa y inflammation.